title: The impact of dietary magnesium restriction on magnesiotropic and calciotropic genes.
abstract: BACKGROUND
  Magnesium (Mg(2+)) is an essential electrolyte with important physiological functions. Consequently, hypomagnesaemia, an electrolyte disorder frequently diagnosed in critically ill patients, can have life-threatening consequences. The kidney plays a central role in the regulation of the Mg(2+) balance. The present study investigated the molecular consequences of dietary Mg(2+) restriction on renal Mg(2+) transporters.
  
  
  METHODS
  Two groups of 10 mice were fed a Mg(2+)-deficient diet or a Mg(2+)-enriched diet for 2 weeks. Serum and urine electrolyte concentrations were assayed. Next, renal mRNA expression levels of Mg(2+)-related genes were measured to determine their sensitivity to the dietary Mg(2+) content. Subsequently, parvalbumin (PV) and the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), both co-expressed in the distal convoluted tubule (DCT) with TRPM6, were further analysed at the protein level using immunoblotting and immunohistochemistry.
  
  
  RESULTS
  Serum and urine electrolyte measurements revealed that dietary Mg(2+) restriction resulted in significant reduction of serum Mg(2+) and Ca(2+) levels, and that the urinary excretion of these ions was also markedly reduced, while phosphate (Pi) excretion was significantly increased. In addition, the serum FGF23 level was markedly increased, whereas Pi was not significantly changed in the Mg(2+)-restricted mouse group. The renal abundance of hepatocyte nuclear factor 1 homeobox B (HNF1B) and the epithelial Mg(2+) channel TRPM6 were increased in response to dietary Mg(2+) restriction, whereas other magnesiotropic transporters were not affected. PV abundance was upregulated, while NCC was significantly downregulated. Furthermore, the expression levels of the epithelial Ca(2+) channel TRPV5 and calbindin-D28K were markedly reduced in the low Mg(2+) group.
  
  
  CONCLUSIONS
  Our data indicate an essential adaptive role for DCT during hypomagnesaemia since TRPM6, HNF1B, PV and NCC expression levels were adjusted. Moreover, hypomagnesaemia resulted in severe changes in Ca(2+) and Pi reabsorption and expression levels of calciotropic proteins.
authors.affiliation: Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Annelies A
authors.initials: AA
authors.lastname: van Angelen
authors.forename: Pedro
authors.initials: P
authors.lastname: San-Cristobal
authors.forename: Wilco P
authors.initials: WP
authors.lastname: Pulskens
authors.forename: Joost G
authors.initials: JG
authors.lastname: Hoenderop
authors.forename: René J
authors.initials: RJ
authors.lastname: Bindels
mesh_terms: D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics; D003106:Colon / Q000378:metabolism; D004032:Diet; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism; D008274:Magnesium / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D049992:Sodium Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics; D014883:Water-Electrolyte Imbalance / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D053503:Epithelial Sodium Channels; C000717428:Fgf23 protein, mouse; C496496:Hnf1b protein, mouse; D010320:Parvalbumins; D012333:RNA, Messenger; D011955:Receptors, Drug; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050053:TRPM Cation Channels; C530168:Trpm6 protein, mouse; C064415:thiazide receptor; D051539:Hepatocyte Nuclear Factor 1-beta; D000089703:Fibroblast Growth Factor-23; D008274:Magnesium
keywords: Ca2+-sensing receptor; electrolyte disturbances; hypomagnesaemia; mouse; parvalbumin